Captopril compared with other antirenin system agents in hypertensive patients: Its triphasic effects on blood pressure and its use to identify and treat the renin factor

Four different pharmacologlc probes (propranolol, saralasin, teprotide, and captopril) hare exposed and characterized the active participation of the renin system in sustaining the derated blood pressure (BP) of most essential hypertension (I.e., the high and "normal" renin forms). Research indicates that renin measurements can be used to predict the effects of these drags on BP, since control plasma renin actirity levels correlate closely with reductions in pressure. Therefore, the renin assay provides a reliable estimate of angiotensin-mediated rasoconstriction, the normalcy of which is gauged by relating it to the urinary sodium excretion, an index of intake and balance. The effects of continued oral administration of captopril closely resemble those previously described with the Intravenously administered nonapeptide-converting enzyme inhibitor, teprotide. Correlations between the induced antibypertensive effect and control plasma renin levels for 89 and 100 different patients receiving either teprotide or captopril alone were 0.82 and 0.89 respectively. The fact that captopril, like the other three antirenln-system drugs, was inactive in low renin states, including in primary aldosteronism and anephric patients, verifies the view that its main antibypertensive action is mediated via renin system blockade. The BP response of untreated patients 90 minutes after an oral dose of captopril can be predictive of its long-term effectiveness. Of practical relevance is a transient rebound of BP observed in the first few days of continuous therapy, with pressures sometimes returning near control levels. This rebound usually subsides by 7 days. Captopril produces continued suppression of the renin system as evidenced by reduced plasma aldosterone levels. But the system retains a capacity to override drag blockade in response to physiologic stimuli. The great potency with specificity of captopril is expressed by its correction of hypertension with few side effects. The cumulative experience with this and earlier pharmacologic probes has opened the door to new approaches in diagnosis and therapy based on analysis of renin system behavior. It also points the way to new research to determine why the renin system so often participates in essential hypertension and to define other pressor factors that might operate when renin and sodium factors are absent or blocked.